There are 1.3 to 1.7 billion people in the world (about 2%-3% of the world's population) chronically infected with the hepatitis C virus (HCV). Hepatitis C is one of the major etiologies of liver disease and liver cancer. In developed countries, the antibody of the hepatitis C virus occurs in a range of 1%-2%. In some areas with a high prevalence of hepatitis C, the occurrence can be above 20%. A mixture of therapies with long efficacy interferon (say IFN-α) and ribavirin are used in current clinical treatments. In addition, a treatment for patients with sustained virologic response (SVR) of chronic hepatitis C is done clinically in general according to the genotype of the virus or host and a combination of IFN/ribavirin. The ratio of this treatment could reach 50%-85%. About 3%-4% of the population suffers from hepatitis C in our country. However, the therapeutic efficacy of treatment using the combination of IFN/ribavirin is only about 70%; not only does the treatment course continue for 6-12 months, but it is also accompanied by substantial side effects, and the patient's daily life is severely affected.
Because the expression level of miRNA is associated with diseases, quantitative analysis of miRNA can be a means to reveal the mechanism of diseases as a target of new drug development. In previous studies, it was found that miR-122, one of the micro ribonucleic acids in a vertebrate, is combined with two positions in the genome of the hepatitis C virus, which strongly facilitates the replication of the virus. Hence, if one realizes the specificity of the genome of the hepatitis C virus to combine with the miR-122 and block the specificity for replication of the virus, it might be possible to relieve the hepatitis C virus infection. Currently a pharmaceutical manufacturer has developed a drug to inhibit the activity of miR-122, which has proceeded to the clinical trial phase.
Some studies suggest that beta-interferons (IFN-β) up regulate certain miRNAs, for example miR-196, miR-296, miR-351, miR-431 and miR-448, and can be combined with predicting sequences in the genome of the hepatitis C virus to reduce its replication and infection. In addition, it was found that expression levels in the members of a Let-7 family are reduced, including lung cancer, hepatocellular carcinoma (HCC), hepatocellular carcinoma and metastatic liver cancer.
Cheng J C et al., Cell Mol Life Sci. 2012 August; 69 (15): 2621-33 once mentioned that Let-7b, which belongs to a family member of the miRNA Let-7, can reduce the expression level of the NS5A gene and a core protein of the hepatitis C virus, and referred to a decreasing expression level of the Let-7b. Combined interferon/ribavirin may have a synergistic inhibitory effect on the luciferase activity in the virus. However, Cheng is silent about whether the Let-7b has effects on interferon stimulated genes (ISGs). In addition, these results are from in vitro experiments, and there are no experiments for practical examples in vivo as evidence.